1. Field of the Invention
There is an increasing interest in improving and varying the capability of preparing antibodies to a wide variety of determinant sites. The use of antibodies has been greatly expanded in diagnostics and therapy. The unique capability of antibodies to bind to a specific determinant site or chemical structure makes them peculiarly useful in directing drugs, radioisotopes, or markers to a particular site in a host. In addition, the ability of antibodies to distinguish a specific structure from similar structures has resulted in their wide use in diagnosis.
Regardless of whether one wishes monoclonal or polyclonal antibodies, the initial step is the immunization of a host. Usually, one hyperimmunizes the host by repeated injections of the immunogen in accordance with a predetermined schedule. Adjuvants are added to potentiate the immune response. Various adjuvants include aluminum and calcium salts, emulsifying adjuvants and bacteria, e.g. mycobacteria and corynebacteria.
In the case of monoclonal antibodies it is particularly desirable to enhance the immune response to specific epitopic sites. Since the preparation of monoclonal antibodies requires the detection of low population events, any technique which enhances the B-lymphocyte population of interest can prove to be important in the production of monoclonal antibodies.
2. Description of the Prior Art
Allison and Gregoriadis, Nature (London) (1974) 252:252; Heath et al., Biochem. Soc. Trans. (1976) 4:129; and Shek and Sabiston, Immunology (1982) 45:349 describe potentiating the immune response by incorporating antigens in liposomes. Shek and Sabiston, Immunology (1982) 47:627; Shek, (1983) Applications of liposomes in immunopotentiation. In: Immunotoxicology, NATO Advanced Study Institute Series (P. W. Mullen, ed.) Springer-Verlag, Heidelberg; and Van Rooijen and Van Nieuwmegen, Immunol. Commun. (1980) 9:243 describe the use of liposomes with immunogens bound to the membrane surface. Leserman et al., Nature (1980) 228:602; Heath et al., Biochem. Biophys. Acta. (1980) 599:42; Heath et al., ibid. (1981) 640:66 and Martin and Papahadjopoulos, J. Biol. Chem. (1982) 257:286 describe the covalent bonding of proteins to lipid vesicles, which disclosure is incorporated herein by reference. See also U.S. Pat. Nos. 4,235,871 and 4,241,046, particularly columns 3-5 of U.S. Pat. No. 4,235,871, which subject matter is incorporated herein by reference.